The overall goal of this collaborative study is to investigate the transmission dynamics of cryptosporidial infections in children in southern India. In developing countries, cryptosporidiosis is a cause, not only of outbreaks, but also of significant endemic disease and morbidity, resulting in diarrheal disease and long-term consequences such as impaired growth and cognitive function. Although cryptosporidiosis is a cause of immediate and prolonged morbidity, the risk factors that affect acquisition of infection in developing countries are not completely understood. In collaborative studies between the Christian Medical College, Vellore, India and the Tufts-New England Medical Center, we propose to use state-of-the-art epidemiological and molecular methodology to investigate the source and spread of infection to children in this area by assessing risks from the external and domestic environment. In this application, our multidisciplinary team will intensively follow two cohorts of children with protected and unprotected drinking water sources in order to quantify the risk of infection from familial, domestic and environmental sources for a period from weaning and for up to two years in a semi-urban slum area of Vellore, South India, where Cryptosporidium is the most common cause of parasitic diarrhea. This study will determine the time to first cryptosporidial infection in children drinking protected and unprotected water, in the context of maternal antibodies, hygiene, water safety and sanitation practices, as well as potentially transmissible infections in family members, household animals, drinking water and sewage. Molecular information on genotyping will be integrated with clinical and epidemiologic information in a spatial database to build integrated models to assess indicators for infection. The underlying hypothesis is that the time to infection with Cryptosporidium spp. in southern India is dependent on environmental risk factors that can be quantified and modeled. This will be the first prospective study of transmission dynamics of cryptosporidiosis using molecular fingerprinting and geospatial technology. This study has important implications for public health because there are no data from longitudinal studies from developing countries using molecular and geospatial methods to asses the role of familial and environmental risk factors in transmission of cryptosporidiosis in children. These data will provide the basis for the logical development of interventions that are appropriate to the developing country communities in which cryptosporidiosis is common.